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Abstract #0628

Radiated Brain Microenvironment Enhances Glioma Growth and Blunts Immunotherapy

Joel Richard Garbow1, Joseph Ackerman1, Chong Duan1, Liya Yuan1, John Engelbach1, Christina Tsien1, and Keith Rich1

1Washington University in St. Louis, Saint Louis, MO, United States

Glioblastoma (GBM) is a highly aggressive, malignant, primary brain tumor. Despite state-of-the-art standard-of-care treatment (surgery, chemotherapy, radiation), GBM inevitably recurs, usually in the peritumoral irradiated tumor/brain interface within two centimeters of the margins of the resection cavity. Anti-PD-L1 (immune checkpoint) inhibitors represent an important new class of cancer treatments, but have shown little efficacy in GBM. In a mouse glioma model, we demonstrate that late evolving effects of radiation blunt the therapeutic effectiveness of anti-PD-L1. Carbogen/O2 gas challenge experiments in these mice six weeks post-irradiation demonstrate that the brain microenvironment is physiologically modified, consistent with the observed blunting of immunotherapy.

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